In understanding any disease process, it is necessary or at least very helpful to understand the expression of specific genes that could be related to the etiology of the disease. With hereditary diseases of the retina, our goal is to determine normal genetic control mechanisms that do not function properly and result in hereditary diseases of the retina such as retinitis pigmentosa or macular degeneration. We have developed new techniques to clone and sequence retina-specific genes by using solid-state subtraction cloning. A number of these genes are either expressed exclusively or predominantly in the retina and can now be thought of as candidate genes in specific ocular hereditary diseases. Some of these genes are a grouping of "stress markers" that denote an oxidative pathway leading to programmed cell death (apoptosis). Similarly, a small number of fatty acid-binding proteins appear to be critical in lipid transport in the retina and are candidate genes in the hereditary disease called Bietti's crystalline dystrophy. On a more general basis, progress has been made in identifying apoptosis as a primary and unifying mechanism for cell death in several hereditary retinal degenerations. Specifically, genes such as clusterin and Heme Oxygenase-1 are markedly increased in the retina as during oxidative stress and appear to be factors that could help to protect retinal cells against insult and death. Use of the genes for these proteins in gene therapy could lead to the treatment of the degenerating neural retina.